Share This

A new approach to drug design, pioneered by a group of researchers at the University of California, San Francisco (UCSF) and Mt. Sinai, New York, promises to help identify future drugs to fight cancer and other diseases that will be more effective and have fewer side effects.

Related Articles

Rather than seeking to find magic bullets -- chemicals that specifically attack one gene or protein involved in one particular part of a disease process -- the new approach looks to find "magic shotguns" by sifting through the known universe of chemicals to find the few special molecules that broadly disrupt the whole diseases process.

"We've always been looking for magic bullets," said Kevan Shokat, PhD, a Howard Hughes Medical Institute Investigator and chair of the Department of Cellular and Molecular Pharmacology at UCSF. "This is a magic shotgun -- it doesn't inhibit one target but a set of targets -- and that gives us a much, much better ability to stop the cancer without causing as many side effects."

Described in the June 7, 2012 issue of the journal Nature, the magic shotgun approach has already yielded two potential drugs, called AD80 and AD81, which in fruit flies were more effective and less toxic than the drug vandetanib, which was approved by the U.S. Food & Drug Administration last year for the treatment of a certain type of thyroid cancer.

Expanding the Targets to Lower a Drug's Toxicity

Drug design is basically all about disruption. In any disease, there are numerous molecular interactions and other processes that take place within specific tissues, and in the broadest sense, most drugs are simply chemicals that interfere with the proteins and genes involved in those processes. The better a drug disrupts key parts of a disease process, the more effective it is.

The toxicity of a drug, on the other hand, refers to how it also disrupts other parts of the body's system. Drugs always fall short of perfection in this sense, and all pharmaceuticals have some level of toxicity due to unwanted interactions the drugs have with other molecules in the body.

Scientists use something called the therapeutic index (the ratio of effective dose to toxic dose) as a way of defining how severe the side effects of a given drug would be. Many of the safest drugs on the market have therapeutic indexes that are 20 or higher -- meaning that you would have to take 20 times the prescribed dose to suffer severe side effects.

Many cancer drugs, on the other hand, have a therapeutic index of 1. In other words, the amount of the drug you need to take to treat the cancer is the exact amount that causes severe side effects. The problem, said Shokat, comes down to the fact that cancer drug targets are so similar to normal human proteins that the drugs have widespread effects felt far outside the tumor.

While suffering the side effects of drugs is a reality that many people with cancer bravely face, finding ways of minimizing this toxicity is a big goal pharmaceutical companies would like to solve. Shokat and his colleagues believe the shotgun approach is one way to do this.

The dogma that the best drugs are the most selective could be wrong, he said, and for cancer a magic shotgun may be more effective than a magic bullet.

Looking at fruit flies, they found a way to screen compounds to find the few that best disrupt an entire network of interacting genes and proteins. Rather than judging a compound according to how well it inhibits a specific target, they judged as best the compounds that inhibited not only that specific target but disrupted other parts of the network while not interacting with other genes and proteins that would cause toxic side effects.

This work was supported by the American Cancer Society, The Waxman Foundation, and the National Institutes of Health -- through grants R01CA109730, R01CA084309, R01EB001987 and P01 CA081403-11.

University of California - San Francisco. "Cancer's next magic bullet may be magic shotgun." ScienceDaily. ScienceDaily, 15 June 2012. <www.sciencedaily.com/releases/2012/06/120615141716.htm>.

University of California - San Francisco. (2012, June 15). Cancer's next magic bullet may be magic shotgun. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2012/06/120615141716.htm

University of California - San Francisco. "Cancer's next magic bullet may be magic shotgun." ScienceDaily. www.sciencedaily.com/releases/2012/06/120615141716.htm (accessed March 3, 2015).

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Feb. 19, 2015 — The journey has been unraveled of two closely related cancer-causing proteins -- one susceptible to the drug Gleevec and one not -- over one billion years of evolution. Researchers pinpointed the ... full story

Dec. 12, 2013 — Taking the breast cancer drug anastrozole for five years reduced the chances of post-menopausal women at high risk of breast cancer developing the disease by 53 percent compared with women who took a ... full story

June 3, 2011 — A drug that targets a specific type of lung cancer shows a dramatic response in more than half of the people who take it. The drug, called crizotinib, has been in clinical trials since 2006, ... full story

Apr. 11, 2011 — A new discovery promises to help physicians identify patients most likely to benefit from breast cancer drug therapies. If the compound, called "Nanobody," proves effective in clinical ... full story

Nov. 10, 2010 — A 'magic bullet' designed by pharmaceutical scientists could eradicate the side effects of a drug used to treat a rare genetic disease. Researchers have chemically modified a drug used to ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.